Tumor-infiltrating CD4 + T cells in patients with gastric cancer

Background T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4 + T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. Materials and methods Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-γ staining assay is conducted. Statistical analysis is performed to show significance. Results The results showed that the percentage of CD4 + T-cells among CD3 + cells in tumors was significantly higher than that in the matched paraneoplastic tissue. CD4 + CD25 high CD127 low regulatory T-cells (Tregs), PD-1 + , Tim-3 + , and PD-1 + Tim-3 + cells were up-regulated on tumor infiltrating T-cells from patients with GC compared to their expressions on corresponding peripheral blood and peritumoral T-cells. Blockades of PD-1 + and Tim-3 + were effective in restoring tumor infiltrating T-cells’ production of interferon-gamma (IFN-γ). Combined PD-1 + and Tim-3 + inhibition had a synergistic effect on IFN-γ secretion by CD4 + T-cells. Conclusion The results suggested that the composition, inhibitors, and location of the immune infiltrate should be considered when evaluating antitumor immunotherapy. A new insight into the mechanisms underlying T cell dysfunction is provided.